Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis

Abstract Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelial cells, with a high rate of recurrence following surgical resection. Recurrence is categorized as early linked to aggressive tumor biology than late recurrence. This study aimed to identify novel peptide m...

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Main Authors: Vasin Thanasukarn, Piya Prajumwongs, Nattha Muangritdech, Watcharin Loilome, Nisana Namwat, Poramate Klanrit, Arporn Wangwiwatsin, Sawanya Charoenlappanit, Janthima Jaresitthikunchai, Sittiruk Roytrakul, Attapol Titapun
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Language:English
Published: Nature Portfolio 2025-01-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-87124-2
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author Vasin Thanasukarn
Piya Prajumwongs
Nattha Muangritdech
Watcharin Loilome
Nisana Namwat
Poramate Klanrit
Arporn Wangwiwatsin
Sawanya Charoenlappanit
Janthima Jaresitthikunchai
Sittiruk Roytrakul
Attapol Titapun
author_facet Vasin Thanasukarn
Piya Prajumwongs
Nattha Muangritdech
Watcharin Loilome
Nisana Namwat
Poramate Klanrit
Arporn Wangwiwatsin
Sawanya Charoenlappanit
Janthima Jaresitthikunchai
Sittiruk Roytrakul
Attapol Titapun
author_sort Vasin Thanasukarn
collection DOAJ
description Abstract Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelial cells, with a high rate of recurrence following surgical resection. Recurrence is categorized as early linked to aggressive tumor biology than late recurrence. This study aimed to identify novel peptide mass fingerprints (PMFs) and potential biomarker panels in the serum of CCA patients with early and late recurrence using mass spectrometry. Serum samples of 81 CCA patients were analyzed using MALDI-TOF MS and LC–MS/MS, with statistical analysis correlating peptide profiles with clinical outcomes like disease-free survival (DFS) and overall survival (OS). A 365-day DFS cut-off effectively distinguished early from late recurrence, with early recurrence linked to poorer survival outcomes. The PMFs from MALDI-TOF MS differentiated recurrence types based on specific mass signatures. LC–MS/MS analysis identified 95 peptides associated with cancer progression in early recurrence and 60 in late recurrence. Distinct protein associations were found: ATR, POLA1, BLM, SP100, and PPP1R15A for early recurrence, and SERPINA1, TGFB2, SERPING1, and CAD for late recurrence, with strong interactions with chemotherapeutic drugs. This study successfully demonstrated the use of PMFs for rapid discrimination between early and late recurrence in CCA and identified potential serum peptide biomarkers to improve accuracy in recurrence classification.
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spelling doaj-art-91c0ac0600ee48d78947e233c2a4dcb02025-01-26T12:29:35ZengNature PortfolioScientific Reports2045-23222025-01-0115111510.1038/s41598-025-87124-2Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysisVasin Thanasukarn0Piya Prajumwongs1Nattha Muangritdech2Watcharin Loilome3Nisana Namwat4Poramate Klanrit5Arporn Wangwiwatsin6Sawanya Charoenlappanit7Janthima Jaresitthikunchai8Sittiruk Roytrakul9Attapol Titapun10Department of Surgery, Faculty of Medicine, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityCholangiocarcinoma Research Institute, Khon Kaen UniversityFunctional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development AgencyFunctional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development AgencyFunctional Proteomics Technology Laboratory, National Center for Genetic Engineering and Biotechnology, National Science and Technology Development AgencyDepartment of Surgery, Faculty of Medicine, Khon Kaen UniversityAbstract Cholangiocarcinoma (CCA) is an aggressive cancer originating from bile duct epithelial cells, with a high rate of recurrence following surgical resection. Recurrence is categorized as early linked to aggressive tumor biology than late recurrence. This study aimed to identify novel peptide mass fingerprints (PMFs) and potential biomarker panels in the serum of CCA patients with early and late recurrence using mass spectrometry. Serum samples of 81 CCA patients were analyzed using MALDI-TOF MS and LC–MS/MS, with statistical analysis correlating peptide profiles with clinical outcomes like disease-free survival (DFS) and overall survival (OS). A 365-day DFS cut-off effectively distinguished early from late recurrence, with early recurrence linked to poorer survival outcomes. The PMFs from MALDI-TOF MS differentiated recurrence types based on specific mass signatures. LC–MS/MS analysis identified 95 peptides associated with cancer progression in early recurrence and 60 in late recurrence. Distinct protein associations were found: ATR, POLA1, BLM, SP100, and PPP1R15A for early recurrence, and SERPINA1, TGFB2, SERPING1, and CAD for late recurrence, with strong interactions with chemotherapeutic drugs. This study successfully demonstrated the use of PMFs for rapid discrimination between early and late recurrence in CCA and identified potential serum peptide biomarkers to improve accuracy in recurrence classification.https://doi.org/10.1038/s41598-025-87124-2CholangiocarcinomaRecurrencePeptidomePeptide biomarkerMALDI-TOF MSLC–MS/MS
spellingShingle Vasin Thanasukarn
Piya Prajumwongs
Nattha Muangritdech
Watcharin Loilome
Nisana Namwat
Poramate Klanrit
Arporn Wangwiwatsin
Sawanya Charoenlappanit
Janthima Jaresitthikunchai
Sittiruk Roytrakul
Attapol Titapun
Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis
Scientific Reports
Cholangiocarcinoma
Recurrence
Peptidome
Peptide biomarker
MALDI-TOF MS
LC–MS/MS
title Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis
title_full Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis
title_fullStr Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis
title_full_unstemmed Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis
title_short Discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through MALDI-TOF MS and LC–MS/MS peptidome analysis
title_sort discovery of novel serum peptide biomarkers for cholangiocarcinoma recurrence through maldi tof ms and lc ms ms peptidome analysis
topic Cholangiocarcinoma
Recurrence
Peptidome
Peptide biomarker
MALDI-TOF MS
LC–MS/MS
url https://doi.org/10.1038/s41598-025-87124-2
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